Junctional Epidermolysis Bullosa

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Clinical Junctional EB

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Inheritance - Herlitz Variant

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Herlitz variant
autosomal recessive;

LAMA3, LAMB3 (80% of mutations), and LAMC2 genes encoding laminin 5 polypepticle chains on 1 q32

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Inheritance - Non Herlitz Variant

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Non Herlitz variant
autosomal recessive; laminin 5 and COL 17A1 on 1 q32 and 1 Oq24, respectively (other mutations identified)

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JEB Pyloric Atresia

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JEB pyloric atresia autosomal recessive; ITGA6 (integrin a6) and ITGB4 (integrin B4) genes on chromosome 2 and I 7q11, respectively

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Incidence

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Approximately 2 to 3 cases per million live births; M=F

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Age at Presentation

Prenatal

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Birth

DNA analysis if mutation in family known; preimplantation determination of genotype at eight cell stage

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Pathogenesis

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Heterogeneous gene mutations encoding proteins at the dermal epidermal junction are responsible for phenotype; basal cell adhesion to the basement membrane is altered resulting in a split within the lamina lucida

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Pathogenesis - Herlitz

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Herlitz LAMA3, LAMB3, LAMC2 gene mutations coding for the polypepticle chains within laminin 5 responsible for anchoring filament development in the lamina lucida

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Pathogenesis - non-Herlitz

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Non Herlitz laminin 5 and COL 17A I (BPI 80 180 kDa bullous pemphigoid anti¬gen) gene mutations, the latter encoding type 17 collagen (hemidesmosome protein the lamina lucida)

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Pathogenesis - JEB with Pyloric Atresia

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JEB with pyloric atresia ITGB4 and ITGA6 mutations encoding a6, B4 integrin, a hemidesmosome transmembrane protein complex

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Clinical Herlitz

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Herlitz Variant
Skin
Generalized bullae without scarring, milia mild atrophy with healing; nonhealing granulation tissue periorally, scalp, neck, upper trunk, nail folds, buttocks, pinnae of the ears

Nails
Absent (shed)

Ear Nose Throat
Dysplastic teeth with enamel defects, oral erosions, laryngeal involvement with hoarseness, croup, edema

Hematologic
Multifactorial anemia

Musculoskeletal
Growth retardation secondary to malnutrition

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Clinical Non-Herlitz

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Non Herlitz Variant
Skin
Bullae increased on extremities, heal with atrophic scarring; worse in warm envi¬ronment

Nails
Dystrophy

Hair
Scarring alopecia Otherwise similar to Herlitz without granulation tissue, anemia, growth retardation and poor prognosis (see Prognosis)

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Clinical JEB with pyloric Atresia

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Junctional EBS Pyloric Atresia
Skin/mucosa
Severe congenital blistering, mucosal erosions

Gastrointestinal
Pyloric atresia

Genitourinary
Hydronephrosis, renail failure secondary to stricture development

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DDx

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other forms of EB (p. 204; 208)
Epidermolytic hyperkeratosis (p.6)
Neonatal HSV
Bullous impetigo
Staphylococcal scalded skin syndrome
Toxic epidermal necrolysis

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Lab

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Bacterial, viral cultures

Skin biopsy for light, electron microscopy, immunofluoresence, cell culture

DNA analysis with blood, buccal swabs

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Management

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Herlitz Variant
See EBS (p. 206), tissue engineered skin grafts, nutritional support, iron supplementation, referral to ophthalmologist; protein and/or gene therapy in the future

Non Herlitz Variant
See EBS

JEB Pyloric Atresia

Referral to surgeon/urologist surgical release of GI/GU strictures, dilatation and gastrostomy

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Prognosis

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Herlitz variant usually fatal by 3 to 4 years of age secondary to profound hypoproteinernia, anemia, and infection

Non Herlitz variant normal life span; bullae may improve with age

JEB pyloric atresia usually fatal early on